ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Rac1 pathway mediates stretch response in pulmonary alveolar epithelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Inhibiting Rac1 signaling alleviates DSS-induced colitis by improving inflammatory response and intestinal permeability.Gastroenterology report · 2025Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- A Peptide Inhibitor of Peroxiredoxin 6 Phospholipase AAntioxidants (Basel, Switzerland) · 2021Article
- Protein kinase R-like endoplasmatic reticulum kinase is a mediator of stretch in ventilator-induced lung injury.Respiratory research · 2018Article
- Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation in ventilator-induced lung injury.Chinese medical journal · 2018Article
- New insights into the mechanisms of pulmonary edema in acute lung injury.Annals of translational medicine · 2018Review
- Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.American journal of respiratory cell and molecular biology · 2017Article
- Expression analysis of platelet-derived growth factor receptor alpha and its ligands in the developing mouse lung.Physiological reports · 2017Article
- Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability.Circulation research · 2017Review
- Superoxide mediates tight junction complex dissociation in cyclically stretched lung slices.Journal of biomechanics · 2016Article
- Local influence of cell viability on stretch-induced permeability of alveolar epithelial cell monolayers.Cellular and molecular bioengineering · 2016Article
- Coming to terms with tissue engineering and regenerative medicine in the lung.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- EHT 1864, a small molecule inhibitor of Ras-related C3 botulinum toxin substrate 1 (Rac1), attenuates glucose-stimulated insulin secretion in pancreatic β-cells.Cellular signalling · 2015Article
- Cecal ligation and puncture accelerates development of ventilator-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Activation of c-Src tyrosine kinase mediated the degradation of occludin in ventilator-induced lung injury.Respiratory research · 2014Article
- Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Potential contribution of type I alveolar epithelial cells to chronic neonatal lung disease.Frontiers in pediatrics · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Alveolar epithelial cells (AECs) maintain the pulmonary blood-gas barrier integrity with gasketlike intercellular tight junctions (TJ) that are anchored internally to the actin cytoskeleton. We have previously shown that AEC monolayers stretched cyclically and equibiaxially undergo rapid magnitude- and frequency-dependent actin cytoskeletal remodeling to form perijunctional actin rings (PJARs). In this work, we show that even 10 min of stretch induced increases in the phosphorylation of Akt and LIM kinase (LIMK) and decreases in cofilin phosphorylation, suggesting that the Rac1/Akt pathway is involved in these stretch-mediated changes. We confirmed that Rac1 inhibitors wortmannin or EHT-1864 decrease stretch-stimulated Akt and LIMK phosphorylation and that Rac1 agonists PIP3 or PDGF increase phosphorylation of these proteins in unstretched cells. We also confirmed that Rac1 pathway inhibition during stretch modulated stretch-induced changes in occludin content and monolayer permeability, actin remodeling and PJAR formation, and cell death. As further validation, overexpression of Rac GTPase-activating protein β2-chimerin also preserved monolayer barrier properties in stretched monolayers. In summary, our data suggest that constitutive activity of Rac1, which is necessary for stretch-induced activation of the Rac1 downstream proteins, mediates stretch-induced increases in permeability and PJAR formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.